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Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo

Kim, Whee-Soo and Min, Sungjin and Kim, Su Kyeom and Kang, Sunghwi and Davis, Hunter and Bar-Zion, Avinoam and Malounda, Dina and Kim, Yu Heun and An, Soohwan and Lee, Jae-Hyun and Bae, Soo Han and Lee, Jin Gu and Kwak, Minsuk and Cho, Seung-Woo and Shapiro, Mikhail G. and Cheon, Jinwoo (2022) Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20220601-257870000

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Abstract

Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes, and is a major goal in the field of mechanobiology. However, existing biosensors for 3D tissue mechanics, primarily based on fluorescent emissions and deformable materials, are limited for in vivo measurement due to the limited light penetration and poor material stability inside intact, living organisms. While magneto-motive ultrasound (MMUS), which uses superparamagnetic nanoparticles as imaging contrast agents, has emerged as a promising modality for real-time in vivo imaging of tissue mechanics, it has poor sensitivity and spatiotemporal resolution. To overcome these limitations, we introduce magneto-gas vesicles (MGVs), a unique class of protein nanostructures based on gas vesicles and magnetic nanoparticles that produces differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid protein nanostructures significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term, and quantitative measurement of mechanical properties within 3D tissues and organs in vivo. We demonstrated the performance of MGV-based mechano-sensors in vitro, in fibrosis models of organoids, and in vivo in mouse liver fibrosis models.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2022.05.26.493158DOIDiscussion Paper
https://www.biorxiv.org/content/10.1101/2022.05.26.493158v1.supplementary-materialPublisherSupporting Information
ORCID:
AuthorORCID
Davis, Hunter0000-0003-1655-692X
Bar-Zion, Avinoam0000-0002-7564-9467
Malounda, Dina0000-0001-7086-9877
An, Soohwan0000-0002-8837-1898
Lee, Jae-Hyun0000-0002-0760-0071
Bae, Soo Han0000-0002-8007-2906
Shapiro, Mikhail G.0000-0002-0291-4215
Cheon, Jinwoo0000-0001-8948-5929
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This work was supported by the Institute for Basic Science (IBS-R026-D1). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government, the Ministry of Science and ICT (MSIT) (No. 2021R1A2C3004262) and Samsung Research Funding & Incubation Center of Samsung Electronics under Project Number SRFC-TC2003-03. M.G.S. is an Investigator of the Howard Hughes Medical Institute (HHMI). This article is subject to HHMI’s Open Access to Publications policy. HHMI Investigators have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. Contributions. W.-S.K. performed overall in vitro and in vivo experiments and analyzed data. S.M designed and performed organoid related experiments. S.K.K., Y.H.K., and S.A. supported hiPSC differentiation, MMUS imaging, and hydrogel characterization, respectively. S.K. provided magnetic nanoparticles. H.D. and A.B. performed initial setup and discussions on this research. D.M. provided gas vesicles. J.-H.L. helped initial setup and discussions on this research. S.H.B. and J.G.L. provided lung tissue for the organoid development. M.K. assisted with the design of research and experiment. W.-S.K and M.K. wrote the manuscript with input from all authors. S.-W.C., M.G.S., and J.C. conceived and supervised the project. Code availability. MATLAB code is available from the corresponding author upon reasonable request. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
Korean Institute for Basic ScienceIBS-R026-D1
National Research Foundation of Korea2021R1A2C3004262
Samsung ElectronicsSRFC-TC2003-0
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
DOI:10.1101/2022.05.26.493158
Record Number:CaltechAUTHORS:20220601-257870000
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220601-257870000
Official Citation:Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo Whee-Soo Kim, Sungjin Min, Su Kyeom Kim, Sunghwi Kang, Hunter Davis, Avinoam Bar-Zion, Dina Malounda, Yu Heun Kim, Soohwan An, Jae-Hyun Lee, Soo Han Bae, Jin Gu Lee, Minsuk Kwak, Seung-Woo Cho, Mikhail G. Shapiro, Jinwoo Cheon bioRxiv 2022.05.26.493158; doi: https://doi.org/10.1101/2022.05.26.493158
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114997
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:01 Jun 2022 22:27
Last Modified:01 Jun 2022 22:27

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